BackgroundBasal cell carcinoma (BCC) is the most common malignancy worldwide, yet the management of patients with advanced or metastatic disease is challenging, with limited treatment options. Recently, programmed death receptor 1 (PD-1) inhibition has demonstrated activity in BCC after prior Hedgehog inhibitor treatment.MethodsWe conducted a multicenter, retrospective analysis of BCC patients treated with PD-1 inhibitor therapy. We examined the efficacy and safety of PD-1 therapy, as well as clinical and pathological variables in association with outcomes. Progression-free survival (PFS), overall survival (OS) and duration of response (DOR) were calculated using Kaplan-Meier methodology. Toxicity was graded per Common Terminology Criteria for Adverse Events V.5.0.ResultsA total of 29 patients with BCC who were treated with PD-1 inhibition were included for analysis, including 20 (69.0%) with locally advanced and 9 (31.0%) with metastatic disease. The objective response rate was 31.0%, with five partial responses (17.2%), and four complete responses (13.8%). Nine patients had stable disease (31.0%), with a disease control rate of 62.1%. The median DOR was not reached. Median PFS was 12.2 months (95% CI 0.0 to 27.4). Median OS was 32.4 months (95% CI 18.1 to 46.7). Two patients (6.9%) developed grade 3 or higher toxicity, while four patients (13.8%) discontinued PD-1 inhibition because of toxicity. Higher platelets (p=0.022) and any grade toxicity (p=0.024) were significantly associated with disease control rate.ConclusionsThe clinical efficacy of PD-1 inhibition among patients with advanced or metastatic BCC in this real-world cohort were comparable to published trial data. Further investigation of PD-1 inhibition is needed to define its optimal role for patients with this disease.

Introduction: The SARS-CoV-2 (COVID-19) pandemic continues in the United States, and patients actively receiving chemotherapy are known to be at enhanced risk for developing symptomatic disease. Our study evaluated the prevalence of COVID-19 among patients and providers of our community-facing county health system during the B1.1.529 (“Omicron”) COVID-19 variant wave. Methods: We retrospectively analyzed patients that received care and clinical providers whom worked at the Jackson Memorial Hospital Hematology/Oncology clinic in Miami, Florida from December 1st, 2021 through April 30th, 2022. After categorizing basic demographic factors for individuals whom tested positive for COVID-19 during the study timeframe, we analyzed additional risk factors leading to COVID-19 positivity including, but not limited to, vaccination status, previous COVID-19 positivity, and active receipt of chemotherapeutics. We then analyzed outcomes related to COVID-19, including treatment with advanced COVID-19 therapies such as oral or intravenous antivirals, monoclonal antibodies, convalescent plasma, steroids, or interleukin-6 inhibitors; interactions with inpatient services including emergency department (ED)/urgent care visits, inpatient and/or ICU admissions, and deaths from COVID-19. We finally assessed quality outcomes such as delay in cancer-directed therapy. This study was approved by the University of Miami IRB and Jackson Health System Clinical Trials Office. Results: 498 patients and 18 providers were retrospectively analyzed during the study timeframe. 49 patients tested positive for COVID-19 (9.84%), while 6 providers tested positive (33.3%) (p = 0.015). Patients whom tested positive were 51.0% female (n = 25), 26.5% Black (n = 13), 73.5% Hispanic/Latinx (n = 36), and 2.05% Asian (n = 1). Only 6.12% patients had tested positive for COVID-19 previously (n = 3), and 42.9% were considered unvaccinated (n = 21) while 14.3% were boosted (n = 7). 73.5% (n = 36) presented with symptomatic disease, 46.9% (n = 23) sought care at an ED/urgent care, 32.6% (n = 13) were admitted to the hospital, 6.12% were admitted to the ICU (n = 3), and 16.3% (n = 8) received advanced therapeutics. There were 2 (8.0%) COVID-19-related deaths (and another outside our study timeframe) among 23 non-COVID-19 related deaths in the patient population (p = 0.75). More than half of the patients whom tested positive experienced a cancer treatment delay (n = 27/49; 55.1%). Conclusions: The prevalence of COVID-19 positivity in our patient cohort during the initial Omicron wave mirrored local, state, and national trends, however a statistically significant greater proportion of our providers tested positive. COVID-19 positivity conferred appreciable disparities in the presentation of disease as well as receipt of cancer treatment. COVID-19 positivity was more likely to result in symptomatic disease and ED/urgent care visit in cancer patients without previous COVID infection and unvaccinated status. COVID-19 accounted for 8.0% of our clinic’s total mortality. Citation Format: Aliya Khan, Samuel A. Kareff, Priscila Barreto-Coelho, Sunil Iyer, Brian Pico, Michele Stanchina, Giselle Dutcher, José Monteiro de Oliveira Novaes, Aparna Nallagangula, Gilberto Lopes. Prevalence of COVID-19 among hematology/oncology patients and providers of a community-facing county health system during the B1.1.529 (“Omicron”) SARS-CoV-2 variant wave [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B123.

Background: Activation in RAS pathway has been associated with cancer development. Three RAS family members, including NRAS, KRAS and HRAS are frequently mutated across various cancer types, where NRAS mutations are present in 15-20% of melanomas. NRAS-mutant melanomas (NRASm) have been extensively characterized. However, molecular and clinical implications of HRAS mutations (HRASm) in melanoma are less well understood. Methods: A total of 6329 melanoma samples were subjected to comprehensive molecular profiling at Caris Life Sciences. Analyses included next generation sequencing of DNA (592 Gene Panel, NextSeq; whole exome sequencing, NovaSEQ), RNA (NovaSeq, whole transcriptome sequencing, WTS) and IHC. MPAS scores to evaluate MAPK pathway activation, IFN scores, QuantiSeq, neoantigen load (high, intermediate, low binding affinity: HBA, IBA and LBA) and GSEA were calculated from mRNA expression data. Wilcoxon, Fisher’s exact were used to determined statistical significance (p value without and q value with multi comparison correction; FDR for GSEA). The reference cohort was the entire melanoma cohort (MC). Results: HRASm were identified in 69 (1.09%) of melanoma samples (hotspots mutations: G13, 40%; Q61, 34%; G12, 18% and others, 9%). HRASm and NRASm had different genomic landscapes: HRASm were significantly associated with a higher mutation rate of NF1 (43.2% vs 27.7%, p<.05), ARID1A (17.2% vs 6.3%, p<.05), B2M (14.3% vs 2.4%, p<.05), RAF1 (12.2% vs 1.4, p<.0001), CTNNB1 (9.1% vs 3.3%, p<.05) and higher amplifications of EMSY (11.8% vs 1.8%, p<.01), MRE11 (4.3% vs 0.5%, p<.05), whereas NRASm harbored less NF1 (14.8% vs 27.7%, q<.0001 ), BRAF (6.9% vs 39.9%, p <.0001), PTEN (3.9% vs 6.9%, q <.05), KIT (0.8% vs 4.4%, q <.0001) mutations and less amplification PDGFR (0.4% vs 1.3%, p<.05), BRAF (0.2% vs 1.4%, p<.05), KIT (0.2% vs 2.1%, q<.05) when comparing to MC. Both HRASm and NRASm had higher MPAS scores than MC (HRASm, 0.24; NRASm, 0.11; MC, -0.41, q<.001). In addition, HRASm showed higher TMB (HRASm, 68.1%; NRASm, 56.9%; MC, 50.0%, q<.05), relatively higher IFN scores (HRASm, 0.16; NRASm, -0.23; MC, -0.24, q = .16) and higher neoantigen load (HBA: HRASm, 10.5; NRASm, 4; MC, 4, p < .05; IBA: HRASm, 17.5; NRASm, 8 MC, 7, p < .05; LBA: HRASm, 37.5; NRASm, 21; MC, 19, p =.1) when compared to NRASm and MC. Lastly, suppression of angiogenesis pathway was observed in both HRASm (NES = 1.7, FDR<.05) and NRASm with respect to MC (NES = 1.4, FDR<.25). Conclusions: The genomic landscape of HRASm are significantly different from that of NRASm, implying their distinct roles in tumorigenesis. HRASm also demonstrated higher MAPK activation, suggesting that they could potentially benefit from agents targeting on this pathway. In addition, HRASm displayed more immunogenic features, associated with down-regulation of angiogenesis pathway, revealing a potential higher susceptibility of HRASm to immunotherapy. Citation Format: Leonel F. Hernandez-Aya, Estelamari Rodriguez, Aparna Nallagangula, Jun Yin, Phillip Walker, Joanne Xiu, Justin Moser, Gino K. In, David Spetzler, Geoffery T. Gibney, Matthew Oberley, Thuy Phung, Michael Atkins, Dave S. Hoon, Wolfgang Michael Korn, Jose Lutzky, Gilberto Lopes. Molecular and immunologic characterization of HRAS mutations in a cohort of 6,329 patients with cutaneous melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5625.